Methyl Acrylate → 6'-Isobutoxyspiro[cyclohexane-1,2'-indene]-1',4(3'H)-dione

HRID 1467918

Reaction equation

HRID 1467918 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7]3([CH2:16][CH2:15][CH:14]([O:17]C)[CH2:13][CH2:12]3)[C:8]2=[O:11])=[CH:4][CH:3]=1.[C:19]([O:23]C)(=O)[CH:20]=[CH2:21].[CH3:25]C(C)([O-])C.[K+].[OH-].[K+]>[Cl-].[Na+].O.O>[CH2:19]([O:23][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7]3([CH2:12][CH2:13][C:14](=[O:17])[CH2:15][CH2:16]3)[C:8]2=[O:11])=[CH:4][CH:3]=1)[CH:20]([CH3:21])[CH3:25]

Participants

7

Reactant 4

HCID 7294Methyl AcrylateHCID 14797Potassium HydroxideHCID 23665647Potassium tert-butoxide2×HCID 581972636'-bromo-4-methoxyspiro[cyclohexane-1,2'-inden]-1'(3'H)-one2×

Product 1

HCID 679793196'-Isobutoxyspiro[cyclohexane-1,2'-indene]-1',4(3'H)-dioneYield 56.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of 6-isobutoxy-2,3-dihydro-1H-inden-1-one (Intermediate 4, 17.4 g, 85 mmol) and methyl acrylate (16.9 mL, 187 mmol) in 2-Me THF (84 mL) cooled to 0° C. was added potassium tert-butoxide (11.8 g, 102 mmol) in portions over 3 min. After stirring at r.t. for 2.5 h more potassium tert-butoxide (2.95 g, 25.5 mmol) was added at 0° C. After stirring at r.t. for 2.5 h were water (126 mL) and potassium hydroxide (4.77 g, 85 mmol) added and the mixture was heated at reflux overnight. The mixture was allowed to cool to r.t. and brine was added. The layers were separated and the aqueous layer was re-extracted with EtOAc twice. The combined organic layers were dried over Na2SO4, filtered and evaporated to yield the title compound (13.7 g, 56% yield). 1H NMR (400 MHz, CDCl3) δ ppm 1.04 (m, 8 H) 1.86 (m, 2 H) 2.11 (dt, 1 H) 2.21 (m, 2 H) 2.47 (m, 3 H) 2.70 (m, 2 H) 3.15 (s, 2 H) 3.76 (m, 3 H) 7.20 (m, 1 H) 7.25 (m, 1 H) 7.38 (d, 1 H); MS (ES+) m/z 287 [M+H]+.

Workup

  1. additionwas added at 0° C
  2. additionadded
  3. temperaturethe mixture was heated
  4. temperatureat reflux overnight
  5. temperatureto cool to r.t.
  6. customThe layers were separated
  7. extractionthe aqueous layer was re-extracted with EtOAc twice
  8. dry with materialThe combined organic layers were dried over Na2SO4
  9. filtrationfiltered
  10. customevaporated

Sources & evidence

ORD record
ord-a86c3bc729b4494fb698878e16cc1a46
Source dataset
uspto-grants-2015_04
Patent number
US09000182B2

Linked notes

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